Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function.
Fragile X syndrome is the most common inherited form of cognitive deficiency in humans and perhaps the best-understood single cause of autism. A trinucleotide repeat expansion, inactivating the X-linked FMR1 gene, leads to the absence of the fragile X mental retardation protein. FMRP is a selective RNA-binding protein that regulates the local translation of a subset of mRNAs at synapses in response to activation of Gp1 metabotropic glutamate receptors (mGluRs) and possibly other receptors. In the absence of FMRP, excess and dysregulated mRNA translation leads to altered synaptic function and loss of protein synthesis-dependent plasticity. Recent evidence indicates the role of FMRP in regulated mRNA transport in dendrites. New studies also suggest a possible local function of FMRP in axons that may be important for guidance, synaptic development, and formation of neural circuits. The understanding of FMRP function at synapses has led to rationale therapeutic approaches.
Bassell
Gary J
GJ
Department of Cell Biology and Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA. gbassel@emory.edu
Warren
Stephen T
ST
D000818:Animals; D001693:Biological Transport, Active / Q000235:genetics; D001921:Brain / Q000002:abnormalities / Q000378:metabolism* / Q000503:physiopathology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D016501:Neurites / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*
D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C497683:FMR1 protein, human; C104077:metabotropic glutamate receptor type 1